The RPS20 gene has been associated with a predisposition to colorectal cancer, typically presenting as early-onset disease with few or no colon polyps. Because this condition is still newly characterized, cancer risk estimates are evolving, but families with RPS20 variants often show a strong history of colorectal cancer across generations. Management generally focuses on early and frequent colonoscopic surveillance, beginning well before the youngest diagnosis in the family, to allow for timely detection and removal of precancerous lesions. Pathogenic variants (disease-causing) in the RPS20 gene are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in RPS20 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
